A deep dive into four thyroglobulin immunoassays from analytical perspective

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Backgrounds Serum thyroglobulin immunometric assays (sTg) are crucial for monitoring differentiated thyroid cancer (DTC) treatment. However, challenges such as anti-thyroglobulin autoantibodies (TgAb) and assay variability hinder evaluations. This study assessed four sTg methods—three second-generation (Architect, Access, Elecsys) and one first-generation (Immulite)—following Clinical and Laboratory Standards Institute (CLSI) and American Thyroid Association (ATA) guidelines. Methods The study compared sTg(Architect), sTg(Access), sTg(Elecsys), and sTg(Immulite). Precision was evaluated per CLSI EP05-A3, while the lower limits of detection (LLD) were assessed using EP17-A2. Passing–Bablok and Bland–Altman analyses were conducted as per EP09c, and semi-quantitative comparisons used Kappa statistics. Results The second-generation sTgs (Architect, Access, Elecsys) exhibited satisfactory precision (<7% coefficient of variation, CV%), unlike sTg(Immulite), which showed significant deviations and inadequate sensitivity for DTC recurrence (Limit of quantitation, LoQ = 4.59 μg/L). Second-generation sTgs had strong correlations (r > 0.884) across all concentration ranges (≤1, 1-10, >10 μg/L), with biases (slope: 1.131-2.027). sTg(Immulite) correlated well with second-generation methods for concentrations >10 μg/L (r > 0.945) but less so for <10 μg/L (r < 0.642). TgAb significantly impacted sTg(Immulite). Kappa statistics revealed strong agreement among second-generation methods (κ > 0.800) but lower concordance with sTg(Immulite), especially in TgAb(+) samples (κ: 0.562-0.653). Agreement ratios were high for second-generation methods (0.667-1.000) but variable for sTg(Immulite), particularly at lower concentrations and in TgAb(+) cases (0.097-0.727). Conclusions sTg(Immulite) did not meet LLD and precision criteria for DTC monitoring, facing issues with TgAb interference. Second-generation sTgs demonstrated consistent performance across all concentrations.